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The Relationship Between Type 2 Diabetes Mellitus and Failure to Proton Pump Inhibitor Treatment in Gastroesophageal Reflux Disease

Hershcovici, Tiberiu MD*,†; Jha, Lokesh K. MD*,†; Gadam, Rakshith MD*,†; Cui, Haiyan PhD; Gerson, Lauren MD, MSc§; Thomson, Stephen MD; Fass, Ronnie MD*,†

Journal of Clinical Gastroenterology: September 2012 - Volume 46 - Issue 8 - p 662–668
doi: 10.1097/MCG.0b013e31824e139b
ALIMENTARY TRACT: Original Articles

Background: There is limited information regarding the contribution of diabetes mellitus (DM) to proton pump inhibitor (PPI) failure in gastroesophageal reflux disease (GERD) patients.

Aim: To determine whether type 2 DM is a risk factor for PPI failure and the potential predictive factors for PPI failure among type 2 DM patients with GERD.

Design: A case-control study was performed using hospital medical records of GERD patients treated with a PPI. The prevalence of type 2 DM and other risk factors (established >1 y before study enrollment) was determined in the PPI failure (treatment with more than once daily PPI) as compared with PPI responders.

Results: A total of 732 GERD patients receiving PPI therapy, including 285 who failed PPI treatment, were included. The overall prevalence of PPI failure was significantly higher in diabetic versus nondiabetic patients. The relationship between PPI failure and type 2 DM depended on body mass index. Only in obese patients the odds ratio of PPI failure was significantly higher in type 2 DM as compared with non-DM patients. In the subgroup of GERD patients with type 2 DM (n=349), PPI failure was significantly associated with female sex, the presence of general comorbidities, and adequate DM control. Duration of DM, type of antidiabetic medication prescribed, and DM-associated complications were not associated with PPI failure.

Conclusions: PPI failure was significantly associated with type 2 DM in obese patients. Among GERD patients with type 2 DM, failure of PPI treatment was significantly associated with female sex and the presence of general comorbidities.

*Neuroenteric Clinical Research Group

Section of Endocrinology, Southern Arizona VA Health Care System

University of Arizona Health Sciences Center

Arizona Cancer Center, Tucson, AZ

§Division of Gastroenterology, Stanford University School of Medicine, Stanford, CA

Declaration of Personal Interest for Ronnie Fass, MD: Research: AstraZeneca; Speaker: Takeda, Nycomed; Advisor: Vecta, Xenoport, Shire, Given Imaging, Reckitt-Benckiser; Lauren Gerson: Research-Santarus, consultant, Takeda, Xenoport.

The remaining authors declare that they have nothing to disclose.

Reprints: Ronnie Fass, MD, Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System, 3601 S. 6th Avenue (1-111-GI), Tucson, AZ 85723-0001 (e-mail:

Received July 12, 2011

Accepted February 1, 2012

© 2012 Lippincott Williams & Wilkins, Inc.